Results 111 to 120 of about 56,603 (238)

Targeting WEE1 in ARID1A/TP53 Concurrent Mutant Colorectal Cancer by Exploiting R‐Loop Accumulation and DNA Repair Deficiencies

open access: yesAdvanced Science, EarlyView.
ARID1A, a SWI/SNF complex component, is frequently mutated in colorectal cancer (CRC). CRC with ARID1A/TP53 concurrent mutations shows marked sensitivity to WEE1 inhibition. ARID1A loss induces R‐loop‐mediated replication stress, impairs ATF3 transcription, and amplifies WEE1i‐induced DNA damage, suggesting a promising therapeutic vulnerability ...
Chi Zhang   +17 more
wiley   +1 more source

Beyond Catalytic Therapy: Copper‐Paeonol Nanozymes Disrupt Fascin‐Mediated Actin Bundling to Suppress Tumor Growth and Metastasis

open access: yesAdvanced Science, EarlyView.
Copper‐paeonol nanozymes target tumor‐specific reactive oxygen species generation and disrupt fascin‐mediated actin bundling, effectively suppressing tumor growth and metastatic colonization. Abstract Fascin, an actin‐bundling protein universally upregulated in metastatic tumors, drives tumor migration and invasion by promoting filopodia and ...
Peiying Zhang   +8 more
wiley   +1 more source

Construction of PANoptosis‐Inhibiting Carbonized Polymer Dots via Machine Learning Potential for Mitigating Chemodrug‐Induced Nephrotoxicity

open access: yesAdvanced Science, EarlyView.
An enhanced sampling method is developed for molecular dynamics based on trained machine learning force fields to guide the construction of PANoptosis‐inhibiting carbonized polymer dots (Lu‐CDs) derived from a flavonoid compound for treating chemodrug‐induced nephrotoxicity.
Xinchen Liu   +8 more
wiley   +1 more source

Bimetallic Peroxide Nanocomposites‐Driven Redox Dyshomeostasis to Activate Sequential Cuproptosis and Pyroptosis for Amplified Tumor Immunotherapy

open access: yesAdvanced Science, EarlyView.
Hyaluronic acid‐modified bimetallic peroxide nanocomposites (MgO2‐CuO2@HA) are designed for synergistic tumor therapy. The nanocomposites release Mg2+, H2O2, and Cu2+ in tumor cells, induce cuproptosis via Cu+‐mediated protein aggregation, and activate pyroptosis through caspase‐1/gasdermin D pathways for inducing immunogenic cell death, collectively ...
Guanting He   +8 more
wiley   +1 more source

Hepatocyte Mettl3 Deficiency Drives Primary Sclerosing Cholangitis and Liver Fibrosis via Cholangiocyte‐Macrophage Crosstalk

open access: yesAdvanced Science, EarlyView.
Schematic illustration demonstrating that hepatic Mettl3 depletion significantly elevates the secretion of Mif and Csf1. This elevation facilitates Trem2+ macrophage infiltration and triggers cholangiocyte remodeling through the Spp1‐Cd44 interaction, resulting in spontaneous PSC development in vivo.
Wenting Pan   +19 more
wiley   +1 more source

Dipiperazine‐Phenyl Derivatives Based on Convergent Molecular Platforms Can Reverse Multidrug Resistance in Gram‐Negative Bacteria by Inhibiting Efflux and Permeabilizing Cell Membranes

open access: yesAdvanced Science, EarlyView.
By integrating a convergent molecular platform strategy, this study designed a novel dual‐target C5 to combat multidrug‐resistant Gram‐negative bacteria. C5 synergistically enhances antibiotic efficacy by inhibiting efflux pumps and increasing bacterial membrane permeability.
Jiale Dong   +11 more
wiley   +1 more source

Host‐Directed Antiviral Activity of SB2960 Through Selective Induction and Remodeling of Stress Granules

open access: yesAdvanced Science, EarlyView.
Amid the ongoing threat of emerging viral pathogens, host‐directed antivirals offer a strategy to overcome viral mutation and drug resistance. SB2960, a small‐molecule inducer of stress granules (SGs), exhibits potent broad‐spectrum antiviral activity with minimal cytotoxicity.
Wan Gi Byun   +14 more
wiley   +1 more source

Cleavage‐Resistant CYLD Protects Against Autoimmune Hepatitis

open access: yesAdvanced Science, EarlyView.
Proteolytic cleavage of the deubiquitinase CYLD emerges as a critical driver of autoimmune hepatitis. TNFα‐induced CYLD loss in macrophages amplifies S100A9‐triggered MAPK activation, leading to excessive chemokine production and hepatic inflammation. Pharmacological inhibition of MEK signaling effectively attenuates experimental disease, highlighting ...
Han Liu   +13 more
wiley   +1 more source

Metabolic Reprogramming of T Cells by Dual UCP2 and IL‐17 Blockade Enhances Immunity Against Pancreatic Cancer

open access: yesAdvanced Science, EarlyView.
This study demonstrates that dual UCP2/IL‐17 blockade reprograms T‐cell metabolism to overcome PDAC immunosuppression. Genipin‐mediated UCP2 inhibition enhances CD8⁺ T‐cell IFN‐γ via IL‐12R/STAT4/mTOR signaling and mitochondrial OXPHOS. Combined IL‐17 depletion amplifies Tc1/Th1 responses, reduces MDSCs, and prolongs survival in PDAC models ...
Chuan‐Teng Liu   +11 more
wiley   +1 more source

WDR5‐H3K4me3 Epigenetic Axis Promotes TRMT6‐Dependent tRNA M1A Modification to Facilitate Triple‐Negative Breast Cancer Progression by Suppressing Ferroptosis

open access: yesAdvanced Science, EarlyView.
Upregulated TRMT6 forms aberrant hypermethylation of a specific tRNA pool and serves as a predictor of poor prognosis in TNBC. This m1A modification in tRNAs enhances translation of FTH1 and FTL, reducing the pool of bioavailable Fe2⁺. Reduced Fe2+ availability impairs RSL3‐induced lipid peroxidation and tumor progression.
Yuqing Lei   +12 more
wiley   +1 more source

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